A phase I study of oral uracil/ftorafur (UFT) plus leucovorin and bis- acetato-ammine-dichloro-cyclohexylamine-platinum IV (JM-216) each given over 14 days every 28 days

Mark D. DeMario, Mark J. Ratain, Nicholas J. Vogelzang, Sridhar Mani, Everett E. Vokes, Gini F. Fleming, Kimberly Melton, Sheryl Johnson, Steven Benner, David Lebwohl

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Purpose: To determine the feasibility, maximal tolerated doses, and response rates for a combined regimen of the platinum and 5-fluorouracil oral analogues bis-acetato-ammine-dichloro-cyclohexyl-amine platinum(IV) (JM-216) and uracil/ftorafur (UFT) coadministered as a 14 consecutive-day every 28- day schedule. Methods: Of 20 patients enrolled in this investigation, 17 on the following dose escalation scheme were evaluable for toxicity and/or response: I UFT 300 mg/day, JM-216 5 mg/day (three patients), II UFT 300 mg/day, JM-216 10 mg/day (four patients), III UFT 300 mg/day, JM-216 20 mg/day (ten patients). Results: All 17 evaluable patients were evaluable for toxicity. At dose level III, dose-limiting nausea and emesis were observed in one patient despite maximal antiemetic support. Importantly, neurotoxicity and nephrotoxicity were not observed at the JM-216 dose levels examined in this study. This observation is consistent with results seen with single agent JM-216. Conclusion: For JM-216 and UFT administered at 20 mg/day and 300 mg/day over 14 days, nausea and emesis were observed as the principal dose-limiting toxicities. These doses are considerably below the maximally tolerated doses of single agent JM-216 and UFT. Shorter administration schedules should be explored in an attempt to increase the dose intensity and minimize the toxicity of this combination oral regimen.

Original languageEnglish (US)
Pages (from-to)385-388
Number of pages4
JournalCancer Chemotherapy and Pharmacology
Volume43
Issue number5
DOIs
StatePublished - 1999
Externally publishedYes

Fingerprint

Cyclohexylamines
Tegafur
Uracil
Leucovorin
Platinum
Toxicity
Maximum Tolerated Dose
Nausea
Vomiting
Appointments and Schedules
Antiemetics
satraplatin
Fluorouracil
Amines

Keywords

  • Advanced cancer
  • Hyperemesis
  • JM-216
  • Oral chemotherapy
  • UFT

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Oncology

Cite this

A phase I study of oral uracil/ftorafur (UFT) plus leucovorin and bis- acetato-ammine-dichloro-cyclohexylamine-platinum IV (JM-216) each given over 14 days every 28 days. / DeMario, Mark D.; Ratain, Mark J.; Vogelzang, Nicholas J.; Mani, Sridhar; Vokes, Everett E.; Fleming, Gini F.; Melton, Kimberly; Johnson, Sheryl; Benner, Steven; Lebwohl, David.

In: Cancer Chemotherapy and Pharmacology, Vol. 43, No. 5, 1999, p. 385-388.

Research output: Contribution to journalArticle

DeMario, Mark D. ; Ratain, Mark J. ; Vogelzang, Nicholas J. ; Mani, Sridhar ; Vokes, Everett E. ; Fleming, Gini F. ; Melton, Kimberly ; Johnson, Sheryl ; Benner, Steven ; Lebwohl, David. / A phase I study of oral uracil/ftorafur (UFT) plus leucovorin and bis- acetato-ammine-dichloro-cyclohexylamine-platinum IV (JM-216) each given over 14 days every 28 days. In: Cancer Chemotherapy and Pharmacology. 1999 ; Vol. 43, No. 5. pp. 385-388.
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abstract = "Purpose: To determine the feasibility, maximal tolerated doses, and response rates for a combined regimen of the platinum and 5-fluorouracil oral analogues bis-acetato-ammine-dichloro-cyclohexyl-amine platinum(IV) (JM-216) and uracil/ftorafur (UFT) coadministered as a 14 consecutive-day every 28- day schedule. Methods: Of 20 patients enrolled in this investigation, 17 on the following dose escalation scheme were evaluable for toxicity and/or response: I UFT 300 mg/day, JM-216 5 mg/day (three patients), II UFT 300 mg/day, JM-216 10 mg/day (four patients), III UFT 300 mg/day, JM-216 20 mg/day (ten patients). Results: All 17 evaluable patients were evaluable for toxicity. At dose level III, dose-limiting nausea and emesis were observed in one patient despite maximal antiemetic support. Importantly, neurotoxicity and nephrotoxicity were not observed at the JM-216 dose levels examined in this study. This observation is consistent with results seen with single agent JM-216. Conclusion: For JM-216 and UFT administered at 20 mg/day and 300 mg/day over 14 days, nausea and emesis were observed as the principal dose-limiting toxicities. These doses are considerably below the maximally tolerated doses of single agent JM-216 and UFT. Shorter administration schedules should be explored in an attempt to increase the dose intensity and minimize the toxicity of this combination oral regimen.",
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T1 - A phase I study of oral uracil/ftorafur (UFT) plus leucovorin and bis- acetato-ammine-dichloro-cyclohexylamine-platinum IV (JM-216) each given over 14 days every 28 days

AU - DeMario, Mark D.

AU - Ratain, Mark J.

AU - Vogelzang, Nicholas J.

AU - Mani, Sridhar

AU - Vokes, Everett E.

AU - Fleming, Gini F.

AU - Melton, Kimberly

AU - Johnson, Sheryl

AU - Benner, Steven

AU - Lebwohl, David

PY - 1999

Y1 - 1999

N2 - Purpose: To determine the feasibility, maximal tolerated doses, and response rates for a combined regimen of the platinum and 5-fluorouracil oral analogues bis-acetato-ammine-dichloro-cyclohexyl-amine platinum(IV) (JM-216) and uracil/ftorafur (UFT) coadministered as a 14 consecutive-day every 28- day schedule. Methods: Of 20 patients enrolled in this investigation, 17 on the following dose escalation scheme were evaluable for toxicity and/or response: I UFT 300 mg/day, JM-216 5 mg/day (three patients), II UFT 300 mg/day, JM-216 10 mg/day (four patients), III UFT 300 mg/day, JM-216 20 mg/day (ten patients). Results: All 17 evaluable patients were evaluable for toxicity. At dose level III, dose-limiting nausea and emesis were observed in one patient despite maximal antiemetic support. Importantly, neurotoxicity and nephrotoxicity were not observed at the JM-216 dose levels examined in this study. This observation is consistent with results seen with single agent JM-216. Conclusion: For JM-216 and UFT administered at 20 mg/day and 300 mg/day over 14 days, nausea and emesis were observed as the principal dose-limiting toxicities. These doses are considerably below the maximally tolerated doses of single agent JM-216 and UFT. Shorter administration schedules should be explored in an attempt to increase the dose intensity and minimize the toxicity of this combination oral regimen.

AB - Purpose: To determine the feasibility, maximal tolerated doses, and response rates for a combined regimen of the platinum and 5-fluorouracil oral analogues bis-acetato-ammine-dichloro-cyclohexyl-amine platinum(IV) (JM-216) and uracil/ftorafur (UFT) coadministered as a 14 consecutive-day every 28- day schedule. Methods: Of 20 patients enrolled in this investigation, 17 on the following dose escalation scheme were evaluable for toxicity and/or response: I UFT 300 mg/day, JM-216 5 mg/day (three patients), II UFT 300 mg/day, JM-216 10 mg/day (four patients), III UFT 300 mg/day, JM-216 20 mg/day (ten patients). Results: All 17 evaluable patients were evaluable for toxicity. At dose level III, dose-limiting nausea and emesis were observed in one patient despite maximal antiemetic support. Importantly, neurotoxicity and nephrotoxicity were not observed at the JM-216 dose levels examined in this study. This observation is consistent with results seen with single agent JM-216. Conclusion: For JM-216 and UFT administered at 20 mg/day and 300 mg/day over 14 days, nausea and emesis were observed as the principal dose-limiting toxicities. These doses are considerably below the maximally tolerated doses of single agent JM-216 and UFT. Shorter administration schedules should be explored in an attempt to increase the dose intensity and minimize the toxicity of this combination oral regimen.

KW - Advanced cancer

KW - Hyperemesis

KW - JM-216

KW - Oral chemotherapy

KW - UFT

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